Homocysteine as a Risk Factor in Cardiovascular Disease

  • David E. C. Cole
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 498)


Homocysteine is a naturally occurring, sulphur amino acid of established clinical relevance. Excess homocysteine excretion is characteristic of patients with the rare inborn error of metabolism -- homocystinuria -- a connective tissue disorder with spontaneous, early dislocation of the ocular lens, marfanoid habitus, and mental retardation.[13] Homocystinuria is also characterized by early death due to vaso-occlusive disease, and is accompanied by hemostatic changes consistent with a thrombophilic state. Increased plasma homocysteine is associated with histopathologic evidence of vascular endothelial injury, vascular smooth muscle proliferation, and progressive arterial stenosis. After its identification, homocystinuria was studied by investigators hypothesizing that a milder disturbance of homocysteine metabolism might be a significant factor in common cardiovascular conditions and coagulopathies. It is only recently that strong evidence for this hypothesis has emerged. [8;11]


Homocysteine Level Neural Tube Defect Plasma Homocysteine Folate Supplementation Total Homocysteine 
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  1. 1.
    Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Br Med J. 1998;316:894–898.CrossRefGoogle Scholar
  2. 2.
    Bos GM, den Heijer M: Hyperhomocysteinemia and venous thrombosis. Semin.Thromb.Hemost. 1998;24:387–391.PubMedCrossRefGoogle Scholar
  3. 3.
    Boushey CJ, Beresford SA, Omenn GS, Motulsky AG: A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. J Am Med Assoc 1995;274:1049–1057.CrossRefGoogle Scholar
  4. 4.
    Cole DE, Ross HJ, Evrovski J, Langman LJ, Miner SE, Daly PA, Wong PY: Correlation between total homocysteine and cyclosporine concentrations in cardiac transplant recipients. Clin Chem 1998;44:2307–2312.PubMedGoogle Scholar
  5. 5.
    Czeizel AE, Dudas I: Prevention of the first occurence of neural-tube defects by periconceptional vitamin supplementation. N.Engl.J.Med. 1992;327:1832–1835.PubMedCrossRefGoogle Scholar
  6. 6.
    Francis JL: Laboratory investigation of hypercoagulability. Semin. Thromb.Hemost. 1998;24:111–126.CrossRefGoogle Scholar
  7. 7.
    Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, et al.: Plasma homocysteine as a risk factor for vascular disease: The European concerted action project. J Am Med Assoc 1997;277:1775–1781.CrossRefGoogle Scholar
  8. 8.
    Langman LJ and Cole DEC. Homocysteine: Cholesterol of the 90s? Clin.Chim.Acta. 1999; 286:63–80.PubMedCrossRefGoogle Scholar
  9. 9.
    Malinow MR, Bostom AG, Krauss RM: Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999;99:178–182.PubMedCrossRefGoogle Scholar
  10. 10.
    Malinow MR, Duell PB, Hess DL, Anderson PH, Kruger WD, Phillipson BE, Gluckman RA, Block PC, Upson BM: Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N.Engl.J.Med. 1998;338:1009–1015.PubMedCrossRefGoogle Scholar
  11. 11.
    Miner SES, Evrovski J, Cole DEC: Clinical chemistry and molecular biology of homocysteine metabolism: An update. CIin.Biochem. 1997;30:189–201.Google Scholar
  12. 12.
    MRC Vitamin Study Research Group: Prevention of neural tube defects: Results of the Medical Research Council vitamin study. Lancet 1991;338:131–137.CrossRefGoogle Scholar
  13. 13.
    Mudd SH, Levy HL, Skovby F: Disorders of transsulfuration; in: Scriver CR, Beaudet AL, Sly WS, Valle D (eds): In: The molecular and metabolic bases of inherited disease.(5th ed) New York, McGraw Hill Inc., vol. I, 1995, pp 1279–1327.Google Scholar
  14. 14.
    Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE: Plasma homocysteine levels and mortality in patients with coronary artery disease. N.Engl.J.Med. 1997;337:230–236.PubMedCrossRefGoogle Scholar
  15. 15.
    Oakley GPJ: Eat right and take a multivitamin. N.Engl.J.Med. 1998;338:1060–1061.PubMedCrossRefGoogle Scholar
  16. 16.
    Ray JG: Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease. Arch.Intern.Med. 1998;158:2101–2106.PubMedCrossRefGoogle Scholar
  17. 17.
    Refsum H, Guttormsen AB, Fiskerstrand T, Ueland PM: Hyperhomocysteinemia in terms of steady-state kinetics. Eur.J.Pediatr. 1998;157 Suppl 2:S45–9:S45–S49.CrossRefGoogle Scholar
  18. 18.
    Rosenblatt DS: Inherited disorders offolate transport and metabolism; in: Scriver CR, Beaudet AL, Sly WS, Valle D (eds): The molecular and metabolic bases of inherited disease.(5th ed.) New York, McGraw Hill, 1995, vol. 11, pp 3111–3128.Google Scholar
  19. 19.
    Rosenquist TH, Ratashak SA, Selhub J: Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acid. Proc Nat Acad Sci USA 1996;93:15227–15232.PubMedCrossRefGoogle Scholar
  20. 20.
    Smithells RW, Seller MJ, Harris R, Fielding DW, Schorah CJ, Nevin NC, Sheppard S, Read AP, Walker S, Wild J: Further experience of vitamin supplementation for prevention of neural tube defect recurrences. Lancet 1983;1:1027–1031.PubMedCrossRefGoogle Scholar
  21. 21.
    Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH: Total homocysteine in plasma or serum: methods and clinical applications.. Clin.Chem. 1993;39:1764–1779.PubMedGoogle Scholar
  22. 22.
    Wilson RD, Van Allen MI: SOGC Genetics Committee: Recomendations on the use of folic acid for the prevention of neural tube defects. J Soc Obs Gynecol Can 1993;March Suppl.:41–46.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • David E. C. Cole
    • 1
  1. 1.Departments of Laboratory Medicine & Pathobiology,Medicine and Paediatrics (Genetics)University of TorontoTorontoCanada

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